Prostaglandins and the regulation of female reproductuve function

前列腺素与女性生殖功能的调节

• 批准号: 44276-2006
• 负责人: Fortier, Michel
• 金额: $ 4.07万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363803
• 关键词: Prostaglandins; regulation; female; reproductuve; function

Over the last twenty years, NSERC funding allowed to develop several cell culture models derived from the uterus of different animal species to study the mechanisms involved locally during embryo-maternal communication especially with regard to maternal recognition of pregnancy. Across species, the single most remarkable and best conserved property of endometrial cells is their ability to produce specific prostaglandins (PG). PG production within a single cell can be modulated by sex steroids, trophoblastic interferons (IFNtau), oxytocin and platelet activating factor (PAF). In ruminants, PGF2fÑ produced by the endometrial epithelial cells is responsible for the destruction of the corpus luteum and the return to the cycle. On the other hand, PGE2 is antiluteolytic and plays different roles that favor the establishment of pregnancy. At the time of recognition of pregnancy, the embryo must regulate the production of uterine PGs to prevent luteolysis and the return to a new cycle. We have found that in epithelial cells basal PGF2fÑ production was stimulated by oxytocin but switched to PGE2 by IFNtau. Over the last five years, we have identified the functional PGFsynthase of the bovine endometrium as the aldose reductase AKR1B5, an old enzyme with a new function. We have also been the first to propose a role for the newly discovered PG transporter PGT in endocrine action of PGs in the reproductive system. Finally we have shown that the expression of PG receptors in the uterus and corpus luteum closely matches the pattern of expression of biosynthetic and transport proteins. Our findings lead to a new paradigm for the regulation of PG action during maternal recognition of pregnancy. We want to use the next granting period to provide a novel integrated view of PG action in the bovine reproductive system. We will study these systems using cell cultures and tissues collected in vivo under different physiological conditions.  The production of PGs will be analyzed by EIA and the full array of PG metabolites produced from sn-6 and omega-3 fatty acids by GC/MS-MS. Expression of messenger RNA will be done by real time RT-PCR and Northern analysis and protein levels by Western blotting and IHC.

在过去的二十年中，NSERC资助开发了几种来自不同动物物种子宫的细胞培养模型，以研究胚胎-母体交流过程中涉及的局部机制，特别是关于母体对怀孕的识别。跨物种，子宫内膜细胞最显著和最保守的特性是它们产生特异性前列腺素（PG）的能力。单细胞内PG的产生可由性类固醇、滋养层干扰素（IFNtau）、催产素和血小板活化因子（PAF）调节。在反刍动物中，由子宫内膜上皮细胞产生的PGF2fÑ负责黄体的破坏和恢复循环。另一方面，PGE2具有抗黄体溶解作用，并发挥不同的作用，有利于妊娠的建立。在识别怀孕时，胚胎必须调节子宫pg的产生，以防止黄体溶解和返回到一个新的周期。我们发现，在上皮细胞中，基底PGF2fÑ的生成受到催产素的刺激，但被IFNtau转换为PGE2。在过去的五年中，我们已经确定了牛子宫内膜的功能性PGFsynthase为醛糖还原酶AKR1B5，这是一种具有新功能的旧酶。我们也首次提出了新发现的PG转运体PGT在生殖系统中PG的内分泌作用中的作用。最后，我们发现PG受体在子宫和黄体中的表达与生物合成和转运蛋白的表达模式密切相关。我们的研究结果为母体识别妊娠过程中PG作用的调节提供了一个新的范例。我们希望利用下一个授权期提供PG在牛生殖系统中的作用的一个新的综合观点。我们将使用不同生理条件下的细胞培养物和体内收集的组织来研究这些系统。通过EIA分析PG的产生，并通过GC/MS-MS分析sn-6和omega-3脂肪酸产生的PG代谢物。信使RNA的表达将通过实时RT-PCR和Northern分析进行，蛋白质水平将通过Western blotting和IHC进行。